Directed Chemotherapy Delivery for Leptomeningeal Metastases PI: Lad, Shivanand and McCabe, Aaron Project Summary Leptomeningeal Metastases (LM) is a condition in which cells from a primary solid or hematological tumor metastasize, invade the subarachnoid space, and spread throughout the cerebrospinal fluid (CSF), resulting in seeding of the leptomeninges along the surface of the brain and spinal cord. It represents a late event of cancer progression and the most frequent symptoms include multiple cranial nerve deficits, motor deficits, altered mental status, headache, and radicular pain. There are now 30,000 US cases annually, secondary to over 1 million annual cases of breast and lung cancer, lymphoma and melanoma. There is currently no cure and the outcome is invariably fatal, with median survival of 4-6 weeks if left untreated and 3-6 months with curren therapies. Reduction in tumor burden is the primary goal to extend survival and quality of life. Minnetronix, a medical device development and manufacturing company, proposes this Phase I STTR in collaboration with experts from the Duke Cancer Institute and Neurosurgery Department at Duke University. Phase I will focus on developing Neurapheresis, a cerebrospinal fluid (CSF) processing platform, that will provide rapid and targeted drug delivery with circulation of chemotherapeutic agents. This proposal will demonstrate feasibility using methotrexate (MTX). The objective of the proposed project is to develop a tailored system to deliver lower doses of chemotherapeutics, with less toxicity and maximum bioavailability throughout the subarachnoid space. Specific Aim 1 will focus on conducting in vitro testing using a design matrix tailored for targeted CSF drug delivery and broad distribution and bioavailability. Longevity and mechanical testing will be performed to ensure safety and reliability. Specific Aim 2 will evaluate the in vivo distribution of chemotherapeutic agents and reduction of CSF tumor cells in a validated rabbit LM model. In summary, Neurapheresis is an innovative, new therapeutic option that provides direct access to the CSF and creates active circulation combined with targeted chemotherapy delivery. This treatment is intended to be complementary and does not replace standard of care (SOC) interventions with systemic chemotherapy regimens. Successful completion of this Phase I STTR will provide Minnetronix with the data to justify broader preclinical studies and development of a GLP-quality system for treatment of LM in Phase II. During Phase II, concurrent regulatory, clinical planning, and reimbursement work will be conducted to prepare for an investigational device exemption (IDE) application at the end of Phase II. The long-term goal of the project is to develop a novel therapeutic approach to improve survival for LM patients worldwide.